Evaluation of a single intra-articular injection of autologous protein solution for treatment of osteoarthritis in horses

Alicia L. Bertone Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Alicia L. Bertone in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Akikazu Ishihara Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Akikazu Ishihara in
Current site
Google Scholar
PubMed
Close
 BVSc, PhD
,
Lisa J. Zekas Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Lisa J. Zekas in
Current site
Google Scholar
PubMed
Close
 DVM
,
Maxey L. Wellman Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Maxey L. Wellman in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Katharine B. Lewis Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Katharine B. Lewis in
Current site
Google Scholar
PubMed
Close
 BS
,
Rebecca A. Schwarze Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Rebecca A. Schwarze in
Current site
Google Scholar
PubMed
Close
 BS
,
Andrea R. Barnaba Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Andrea R. Barnaba in
Current site
Google Scholar
PubMed
Close
 BS
,
Michael L. Schmall Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Michael L. Schmall in
Current site
Google Scholar
PubMed
Close
 DVM, MS
,
Peter M. Kanter South Towns Equine, 925 Quaker Rd, East Aurora, NY 14052.

Search for other papers by Peter M. Kanter in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
, and
Ron L. Genovese Cleveland Equine Clinic, 3340 Webb Rd, Ravenna, OH 44266.

Search for other papers by Ron L. Genovese in
Current site
Google Scholar
PubMed
Close
 VMD

Abstract

Objective—To evaluate intra-articular autologous protein solution (APS) for the treatment of osteoarthritis in horses.

Animals—40 client-owned horses with naturally occuring osteoarthritis.

Procedures—APS was generated from a dual-device system that concentrated plasma and WBC proteins and enriched platelet growth factors. Horses were randomly assigned to receive an intra-articular injection of 5 mL of saline (0.9% NaCl) solution (n = 20) or APS (20), exercised on a treadmill, and evaluated on the basis of lameness grades, kinetic gait analysis, joint circumference, and range of motion for 14 days. Horses that received saline solution were administered APS at termination of the study, and clients scored horses for lameness and discomfort before, 12 weeks after, and 52 weeks after the APS injection.

Results—The APS group had significant improvements in lameness grade, asymmetry indices of vertical peak force, and range of joint motion by 14 days, compared with baseline or control group values. No adverse effects associated with APS treatment were evident. Clients assessed lameness and comfort as improved at 12 and 52 weeks. The APS had greater likelihood (OR, 4.3 to 30.0) of a therapeutic response in horses with a lameness score < 4, < 10% vertical force asymmetry, or absence of marked osteophyte formation, subchondral sclerosis, or joint space narrowing. Concentration of interleukin-1 receptor antagonist in APS was 5.8 times that in blood.

Conclusions and Clinical Relevance—Intra-articular administration of APS can be considered an effective treatment option for equine osteoarthritis, with the potential for disease-modifying effects.

Abstract

Objective—To evaluate intra-articular autologous protein solution (APS) for the treatment of osteoarthritis in horses.

Animals—40 client-owned horses with naturally occuring osteoarthritis.

Procedures—APS was generated from a dual-device system that concentrated plasma and WBC proteins and enriched platelet growth factors. Horses were randomly assigned to receive an intra-articular injection of 5 mL of saline (0.9% NaCl) solution (n = 20) or APS (20), exercised on a treadmill, and evaluated on the basis of lameness grades, kinetic gait analysis, joint circumference, and range of motion for 14 days. Horses that received saline solution were administered APS at termination of the study, and clients scored horses for lameness and discomfort before, 12 weeks after, and 52 weeks after the APS injection.

Results—The APS group had significant improvements in lameness grade, asymmetry indices of vertical peak force, and range of joint motion by 14 days, compared with baseline or control group values. No adverse effects associated with APS treatment were evident. Clients assessed lameness and comfort as improved at 12 and 52 weeks. The APS had greater likelihood (OR, 4.3 to 30.0) of a therapeutic response in horses with a lameness score < 4, < 10% vertical force asymmetry, or absence of marked osteophyte formation, subchondral sclerosis, or joint space narrowing. Concentration of interleukin-1 receptor antagonist in APS was 5.8 times that in blood.

Conclusions and Clinical Relevance—Intra-articular administration of APS can be considered an effective treatment option for equine osteoarthritis, with the potential for disease-modifying effects.

Contributor Notes

Supported by Biomet Biologics, the 2011 summer research scholarship at The Ohio State University College of Veterinary Medicine, and the animal science internship program at The Ohio State University.

Presented in abstract form in the proceedings of the American College of Veterinary Surgeons Veterinary Symposium, National Harbor, Md, November 2012. Presented in abstract form at the 3rd North American Veterinary Regenerative Medicine Association Annual Meeting, Savannah, Ga, November 2012.

The authors thank Krista O'Shaughnessey and Jacy Hoeppner for product technical support; Megan Cline, Stephanie Vijan, Jill Stephens, Melissa Roemer, Lauren Eisemann, Rachel Wermertm, and Rebekah Sanchez-Hodge for technical assistance; and Drs. Harold Kemp, Jane Kennedy, Jim Chase, Patricia Balzer, Peter Meuse, Brett Berthold, Chris Beinlich, Don Palmer, Hugh Worsham, John Stanek, Keith Brown, Robert Schwartz, Thomas Beckman, Thomas Walrond, William Gesel, and William Wise for patient referral.

Address correspondence to Dr. Bertone (bertone.1@osu.edu).
  • 1. Rossdale PD, Hopes R, Digby NJ, et al. Epidemiological study of wastage among racehorses 1982 and 1983. Vet Rec 1985; 116: 6669.

  • 2. National Animal Health Monitoring System. Part 1: baseline reference of 1998 equine health and management. Fort Collins, Colo: Centers for Epidemiology and Animal Health, Veterinary Services, APHIS, USDA 1998.

    • Search Google Scholar
    • Export Citation
  • 3. Doucet MY, Bertone AL, Hendrickson D, et al. Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. J Am Vet Med Assoc 2008; 232: 9197.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Frisbie DD, McIlwraith CW, Kawcak CE, et al. Evaluation of topically administered diclofenac liposomal cream for treatment of horses with experimentally induced osteoarthritis. Am J Vet Res 2009; 70: 210215.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Frisbie DD, Kawcak CE, Baxter GM, et al. Effects of 6α-methylprednisolone acetate on an equine osteochondral fragment exercise model. Am J Vet Res 1998; 59: 16191628.

    • Search Google Scholar
    • Export Citation
  • 6. Kawcak CE, Norrdin RW, Frisbie DD, et al. Effects of osteochondral fragmentation and intra-articular triamcinolone acetonide treatment on subchondral bone in the equine carpus. Equine Vet J 1998; 30: 6671.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Todhunter RJ, Freeman KP, Yeager AE, et al. Effects of exercise and polysulfated glycosaminoglycan on the development of osteoarthritis in equine carpal joints with osteochondral defects. Vet Surg 1993; 22: 330342.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Frisbie DD, Kawcak CE, McIlwraith CW, et al. Evaluation of polysulfated glycosaminoglycan or sodium hyaluronan administered intra-articularly for treatment of horses with experimentally induced osteoarthritis. Am J Vet Res 2009; 70: 203209.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Kawcak CE, Frisbie DD, Trotter GW, et al. Effects of intravenous administration of sodium hyaluronate on carpal joints in exercising horses after arthroscopic surgery and osteochondral fragmentation. Am J Vet Res 1997; 58: 11321140.

    • Search Google Scholar
    • Export Citation
  • 10. Caron JP. Intra-articular injections for joint disease in horses. Vet Clin North Am Equine Pract 2005; 21: 559573.

  • 11. Frisbie DD. Future directions in treatment of joint disease in horses. Vet Clin North Am Equine Pract 2005; 21: 713724.

  • 12. Bosch G, van Schie HT, de Groot MW, et al. Effects of platelet-rich plasma on the quality of repair of mechanically induced core lesions in equine superficial digital flexor tendons: a placebo-controlled experimental study. J Orthop Res 2010; 28: 211217.

    • Search Google Scholar
    • Export Citation
  • 13. Bosch G, René van Weeren P, Barneveld A, et al. Computerised analysis of standardised ultrasonographic images to monitor the repair of surgically created core lesions in equine superficial digital flexor tendons following treatment with intratendinous platelet rich plasma or placebo. Vet J 2011; 187: 9298.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Waselau M, Sutter WW, Genovese RL, et al. Intralesional injection of platelet-rich plasma followed by controlled exercise for treatment of midbody suspensory ligament desmitis in Standardbred racehorses. J Am Vet Med Assoc 2008; 232: 15151520.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. DeRossi R, Coelho AC, Mello GS, et al. Effects of platelet-rich plasma gel on skin healing in surgical wound in horses. Acta Cir Bras 2009; 24: 276281.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. Hraha TH, Doremus KM, McIlwraith CW, et al. Autologous conditioned serum: the comparative cytokine profiles of two commercial methods (IRAP and IRAP II) using equine blood. Equine Vet J 2011; 43: 516521.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Frisbie DD, Kawcak CE, Werpy NM, et al. Clinical, biochemical, and histologic effects of intra-articular administration of autologous conditioned serum in horses with experimentally induced osteoarthritis. Am J Vet Res 2007; 68: 290296.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Frisbie DD, Ghivizzani SC, Robbins PD, et al. Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene. Gene Ther 2002; 9: 1220.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Chevalier X, Goupille P, Beaulieu AD, et al. Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 2009; 61: 344352.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Woodell-May J, Matuska A, Oyster M, et al. Autologous protein solution inhibits MMP-13 production by IL-1β and TNFα-stimulated human articular chondrocytes. J Orthop Res 2011; 29: 13201326.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Fahie MA, Ortolano GA, Guercio V, et al. A randomized controlled trial of the efficacy of autologous platelet therapy for the treatment of osteoarthritis in dogs. J Am Vet Med Assoc 2013; 243: 12911297.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Akeda K, An HS, Okuma M, et al. Platelet-rich plasma stimulates porcine articular chondrocyte proliferation and matrix biosynthesis. Osteoarthritis Cartilage 2006; 14: 12721280.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Anitua E, Sánchez M, Nurden AT, et al. Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients. Rheumatology (Oxford) 2007; 46: 17691772.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. van Buul GM, Koevoet WL, Kops N, et al. Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes. Am J Sports Med 2011; 39: 23622370.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Kon E, Buda R, Filardo G, et al. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc 2010; 18: 472479.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Sampson S, Reed M, Silvers H, et al. Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis: a pilot study. Am J Phys Med Rehabil 2010; 89: 961969.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Filardo G, Kon E, Buda R, et al. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2011; 19: 528535.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28. Sánchez M, Guadilla J, Fiz N, et al. Ultrasound-guided platelet-rich plasma injections for the treatment of osteoarthritis of the hip. Rheumatology (Oxford) 2012; 51: 144150.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 2004; 114: 15021508.

    • Search Google Scholar
    • Export Citation
  • 30. Ishihara A, Reed SM, Rajala-Schultz PJ, et al. Use of kinetic gait analysis for detection, quantification, and differentiation of hind limb lameness and spinal ataxia in horses. J Am Vet Med Assoc 2009; 234: 644651.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Kay AT, Bolt DM, Ishihara A, et al. Anti-inflammatory and analgesic effects of intra-articular injection of triamcinolone acetonide, mepivacaine hydrochloride, or both on lipopolysaccharide-induced lameness in horses. Am J Vet Res 2008; 69: 16461654.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Li J, Gorski DJ, Anemaet W, et al. Hyaluronan injection in murine osteoarthritis prevents TGF-beta-induced synovial neovascularization and fibrosis and maintains articular cartilage integrity by a CD44-dependent mechanism. Arthritis Res Ther 2012; 14: R151.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Sutter WW, Kaneps AJ, Bertone AL. Comparison of hematologic values and transforming growth factor β and insulin-like growth factor concentrations in platelet concentrates obtained by use of buffy coat and apheresis methods from equine blood. Am J Vet Res 2004; 65: 924930.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. Yang KG, Raijmakers NJ, van Arkel ER, et al. Autologous interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial. Osteoarthritis Cartilage 2008; 16: 498505.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35. Baltzer AW, Moser C, Jansen SA, et al. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. Osteoarthritis Cartilage 2009; 17: 152160.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36. O'Shaughnessey KM, Panitch A, Woodell-May JE. Blood-derived anti-inflammatory protein solution blocks the effect of IL-1β on human macrophages in vitro. Inflamm Res 2011; 60: 929936.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. Goodrich LR, Hidaka C, Robbins PD, et al. Genetic modification of chondrocytes with insulin-like-growth factor-1 enhances cartilage healing in an equine model. J Bone Joint Surg Br 2007; 89: 672685.

    • Search Google Scholar
    • Export Citation

Advertisement